SITES OF NITRIC-OXIDE (NO) ACTIONS IN CONTROL OF CIRCULAR MUSCLE MOTILITY OF THE PERFUSED ISOLATED CANINE ILEUM

In the isolated intra-arterially perfused canine ileum, NW-nitro-L-arg inine (L-NNA, 3 x 10(-4) M) increased tonic and phasic motor activity of the circular muscle, As has previously been shown, L-Nh:A enhanced contractions to electrical field stimulation at-sites proximal to the serosal electrodes and concerted initial relaxation when present at di stal sites to contraction. L-NNA shifted the acetylcholine dose-respon se curve to the left and amplified the response to low-dose acetylchol ine, Following L-NNA, addition of 10(-5) M sodium nitroprusside (NO do nor) returned the tonic and phasic activity, the electrical field stim ulation responses, and the acetylcholine dose-response curve to contro l values. Tetrodotoxin (TTX, 10(-6) M) increased tone (less than L-NNA ) and abolished responses to both electrical field stimulation and mot or activity induced by prior t-NNA. Subsequent L-NNA did not alter TTX -induced tonic motor responses. TTX also shifted the acetylcholine dos e-response curve leftward and increased the responses to low-dose acet ylcholine. After TTX, sodium nitroprusside returned the low-dose acety lcholine responses to control values and, after L-MNA, failed to resto re them to control values, After L-NNA and TTX, sodium nitroprusside r estored responses to low-dose acetylcholine to control values. Thus, r emoval of inhibition of the release of excitatory neurotransmitters, n ot removal of actions of NO on the muscle, accounted for the increases in tonic and phasic activity from L-NNA. Uninhibited release of excit atory transmitters augmented circular muscle responses to low-dose ace tycholine. TTX eliminated effects of excitatory transmitters, allowing exogenous NO to reduce low-dose acetylcholine contractions. No treatm ent affected the maximum responses to acetylcholine, produced by a con tractile mechanism independent of muscle excitability and unaffected b y exogenous NO or release of neurotransmitters.